Our objectives are to develop mathematical models and computer simulations to examine the interplay among microvasculature rheology, blood chemistry, oxygenation, and red cell sickling, and to relate them to the altered physiology of sickle-cell disease. Particular emphasis will be placed on the investigation of vasculr occlusive crisis. Key components of this crisis model will be derived from studies of rheological and oxygen transport phenomena in the microcirculatory system and the molecular biochemistry of the sicking process. Our research goals have been to investigate: (1) the molecular biochemistry of the sickling process; (2) the fluid mechanics of the microcirculatory system; (3) the polymerization and blood chemistry of HbSS; and (4) hematological compensation, and changes in the erythropoietic system related to sickle cell disease and its treatment.